Permanent damage to the brain is a common sequelae of stroke, trauma and cardiac arrest. Each year in the United States, over 350,000 people experience an out-of-hospital cardiac arrest, and only 6.4% survive until hospital discharge without significant neurological damage. Cardiac arrest is the leading cause of death in the United States, with a direct medical cost of $2 billion per year. Stroke is the third leading cause of death and the leading cause of disability, with the cost of treatment, supportive care and lost productivity estimated at $43 billion per year. There are more than 1.5 million new head injuries in United States each year with an estimated annual cost of $53 billion. About 5.3 million people in the United States (2% of the population) are living with a permanent disability from traumatic brain injury. In spite of the tremendous financial cost and personal suffering caused by these conditions, currently available techniques to reverse cerebral damage have been generally ineffective.
There are well documented cases of incidentally preserved neurological function in drowning victims who have had prolonged cardiac arrest in cold water. Hypothermia can substantially reduce deterioration in hypoxic or anoxic neurological, myocardial or other tissue by slowing some of the thermodynamic tendency toward tissue death and by protecting against reperfusion injury. Tissue cooling can also reduce brain edema that raises intracranial pressure and reduces perfusion of already damaged brain tissue, or reduce swelling of the spinal cord that accompanies traumatic injury. Many other types of inflammation can also be reduced by cooling of affected tissue.
Animal studies have found significantly greater neurological function after cerebral anoxia if the brain is cooled; however human studies have not consistently found this benefit. The reasons for this difference are not well understood, but it is believed that the prolonged time needed to cool the brain using existing clinical methods is partially responsible for a lack of definitive benefits in humans. The depth of cooling may also be a therapeutically limiting factor.
Cerebral hypothermia treatment has previously employed cooling of the entire body to cool the brain. Total body cooling requires cooling of a mass much larger than the head that inherently slows the rate of brain cooling. For example, passive total body cooling by applying cold liquid or a cooling blanket to the skin induces hypothermia, but this approach is slow because of the low surface-to-volume ratio of the skin to the body. In addition, a therapeutically optimal body and brain temperature is often not achieved using these methods. Total body cooling also subjects other organ systems to the same or greater degree of cooling as the brain, risking unwanted systemic effects or damage.
Active total body cooling involves an intervention to more quickly cool the blood or internal body cavities. Such interventions often require highly skilled medical teams to implement them, and initiation of therapy may be significantly delayed due to the invasiveness and complexity of the treatment. Various methods of actively infusing cold liquids into the body have been described but these methods usually require cooling of the entire body in order to effect cooling of the brain. U.S. Pat. No. 5,927,273 discloses a cardiopulmonary resuscitation method in which gas in the lungs is replaced with a cooled oxygen-carrying liquid. U.S. Pat. No. 6,962,601 discloses phase-change perfluorocarbon particulate slurries that can be used to induce hypothermia by administering them internally or circulating them through a cooling cap or blanket.
Localized cooling of various structures in the head has been described but rates of cooling are slow and the desired level of cooling is often not achieved. Devices for enclosing the head in a helmet or shroud that externally circulates cooling fluid around the scalp are shown in U.S. Pat. Nos. 4,920,963; 5,755,756; and 7,052,509. U.S. Patent Publication No. 2007/0123813 discloses a method of cerebral and systemic cooling in which a nebulized liquid is delivered as a mist or spray to the nasal and/or oral cavities of a subject. A similar method is also disclosed in Brown et al., Surgical Forum 15:413-415, 1964, in which a dog's head was immersed in circulating ice water, and large bore catheters were inserted into the nostrils of an animal to perfuse the nasopharynx with ice water at a rate of 1.1 to 1.6 L/min An even more invasive localized hypothermia technique is illustrated in U.S. Pat. No. 7,156,867, which discloses a head-cooling cap and a brain-cooling probe for insertion into the lateral ventricle of the brain. Cooling liquid is infused through the probe into the ventricles of the brain to circulate cooling fluid and cool the brain.
U.S. Pat. No. 7,189,253 introduces cooled liquid through a catheter that is advanced through the nostril of a subject with the tip placed at the level of the back of the tongue. A balloon carried by the catheter is expanded with cold liquid to fill the nasal cavity without allowing the cool liquid to contact the walls of the nasal cavity or the vascular nasal mucosa.
None of these techniques is known to provide the rapid cerebral hypothermia that achieves desired tissue protection, for example against permanent neurological damage following brain insults such as cardiogenic shock, stroke or direct traumatic damage to the brain. The need for an improved device of this nature has been highlighted by recent efforts in the medical community to routinely provide head or body cooling to patients who have had a myocardial infarction, or are undergoing heart surgery, to avoid permanent brain injury. Such cooling methods range from total body immersion in cold liquid to lowering the thermostat in the hospital rooms of patients. However, such interventions have been largely unsuccessful, and many of them have required sophisticated devices and surgical interventions that have limited use of induced hypothermia outside of a hospital setting. There is a need for therapeutic hypothermia techniques that can selectively and rapidly cool the brain or the entire body, and for techniques that are suitable for rapid application outside a hospital under emergency conditions. There is also a need for techniques that can provide for deeper levels of hypothermia in the brain while keeping the body relatively warmer.